NPASS Compound

Natural Product: NPC522614

Natural Product ID	NPC522614
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	2-(4-hydroxy-3-methoxy-phenyl)-7-methoxy-5-[(2~{S},3~{S},4~{S},5~{R},6~{S})-3,4,5-trihydroxy-6-methyl-tetrahydropyran-2-yl]oxy-chromen-4-one
IUPAC Name	2-(4-hydroxy-3-methoxy-phenyl)-7-methoxy-5-[(2~{S},3~{S},4~{S},5~{R},6~{S})-3,4,5-trihydroxy-6-methyl-tetrahydropyran-2-yl]oxy-chromen-4-one
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	n.a.
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000261] Phenylpropanoids and polyketides [CHEMONTID:0000334] Flavonoids [CHEMONTID:0001111] Flavonoid glycosides [CHEMONTID:0001583] Flavonoid O-glycosides

The Chemical Classification was calculated by Classyfire, a software for chemical taxonomy calculation. Reference: DOI:10.1186/s13321-016-0174-y.

Chemical Representations

RDKit 3D 57 60 0 0 0 0 0 0 0 0999 V2000 -1.6126 3.6009 2.6847 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3012 3.1851 2.4602 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.0155 2.0989 1.6393 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0713 1.4411 1.0505 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9210 0.3579 0.2217 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9277 -0.3310 -0.3876 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.2968 -0.1180 -0.3247 C 0 0 2 0 0 0 0 0 0 0 0 0 -3.9393 -1.2128 0.2589 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.2317 -0.8661 0.6248 C 0 0 1 0 0 0 0 0 0 0 0 0 -5.2989 0.2394 1.6227 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.0142 -0.5995 -0.6327 C 0 0 2 0 0 0 0 0 0 0 0 0 -5.9176 -1.7672 -1.4231 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.3713 0.5104 -1.4423 C 0 0 2 0 0 0 0 0 0 0 0 0 -5.9814 0.5360 -2.7033 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.9053 0.2153 -1.6751 C 0 0 2 0 0 0 0 0 0 0 0 0 -3.7005 -0.7651 -2.6140 O 0 0 0 0 0 0 0 0 0 0 0 0 0.4034 -0.0516 0.0031 C 0 0 0 0 0 0 0 0 0 0 0 0 0.6545 -1.1311 -0.8151 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.2662 -1.7601 -1.3716 O 0 0 0 0 0 0 0 0 0 0 0 0 1.9751 -1.5269 -1.0234 C 0 0 0 0 0 0 0 0 0 0 0 0 2.9981 -0.8467 -0.4196 C 0 0 0 0 0 0 0 0 0 0 0 0 4.3993 -1.2391 -0.6192 C 0 0 0 0 0 0 0 0 0 0 0 0 4.7642 -2.2932 -1.4094 C 0 0 0 0 0 0 0 0 0 0 0 0 6.0998 -2.6403 -1.5787 C 0 0 0 0 0 0 0 0 0 0 0 0 7.1048 -1.9378 -0.9589 C 0 0 0 0 0 0 0 0 0 0 0 0 8.4556 -2.2773 -1.1213 O 0 0 0 0 0 0 0 0 0 0 0 0 6.7107 -0.8826 -0.1702 C 0 0 0 0 0 0 0 0 0 0 0 0 7.7110 -0.1454 0.4762 O 0 0 0 0 0 0 0 0 0 0 0 0 7.3706 0.9622 1.3095 C 0 0 0 0 0 0 0 0 0 0 0 0 5.4003 -0.5171 0.0154 C 0 0 0 0 0 0 0 0 0 0 0 0 2.7005 0.1750 0.3504 O 0 0 0 0 0 0 0 0 0 0 0 0 1.4716 0.5954 0.5846 C 0 0 0 0 0 0 0 0 0 0 0 0 1.2765 1.6813 1.4120 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0967 3.9493 1.7342 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2784 2.7809 3.0546 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5980 4.4142 3.4404 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0704 1.8047 1.2577 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5143 0.7475 0.3302 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.6840 -1.7779 1.0956 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5075 0.0872 2.3786 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.2982 1.2549 1.1833 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.2742 0.1670 2.1857 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.0633 -0.3393 -0.4628 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.1665 -2.5631 -0.8593 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.4935 1.4727 -0.9217 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.9909 1.4995 -2.9723 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4136 1.1553 -2.0165 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5122 -1.6342 -2.1969 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1355 -2.3665 -1.6625 H 0 0 0 0 0 0 0 0 0 0 0 0 4.0099 -2.9019 -1.9377 H 0 0 0 0 0 0 0 0 0 0 0 0 6.3758 -3.4849 -2.2131 H 0 0 0 0 0 0 0 0 0 0 0 0 8.6693 -3.2697 -0.9591 H 0 0 0 0 0 0 0 0 0 0 0 0 6.8399 0.6176 2.2188 H 0 0 0 0 0 0 0 0 0 0 0 0 8.2612 1.5611 1.5296 H 0 0 0 0 0 0 0 0 0 0 0 0 6.7155 1.6126 0.6676 H 0 0 0 0 0 0 0 0 0 0 0 0 5.1250 0.3366 0.6569 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1060 2.1862 1.8655 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 3 4 2 0 4 5 1 0 5 6 1 0 6 7 1 0 7 8 1 0 8 9 1 0 9 10 1 0 9 11 1 0 11 12 1 0 11 13 1 0 13 14 1 0 13 15 1 0 15 16 1 0 5 17 2 0 17 18 1 0 18 19 2 0 18 20 1 0 20 21 2 0 21 22 1 0 22 23 2 0 23 24 1 0 24 25 2 0 25 26 1 0 25 27 1 0 27 28 1 0 28 29 1 0 27 30 2 0 21 31 1 0 31 32 1 0 32 33 2 0 33 3 1 0 15 7 1 0 32 17 1 0 30 22 1 0 1 34 1 0 1 35 1 0 1 36 1 0 4 37 1 0 7 38 1 1 9 39 1 1 10 40 1 0 10 41 1 0 10 42 1 0 11 43 1 1 12 44 1 0 13 45 1 1 14 46 1 0 15 47 1 6 16 48 1 0 20 49 1 0 23 50 1 0 24 51 1 0 26 52 1 0 29 53 1 0 29 54 1 0 29 55 1 0 30 56 1 0 33 57 1 0 M END

Standard InCHIKey	LMRIAWFGTGLXRL-CSTZPELOSA-N
Standard InCHI	InChI=1S/C23H24O10/c1-10-20(26)21(27)22(28)23(31-10)33-18-8-12(29-2)7-17-19(18)14(25)9-15(32-17)11-4-5-13(24)16(6-11)30-3/h4-10,20-24,26-28H,1-3H3/t10-,20-,21-,22-,23-/m0/s1
SMILES	COC1=CC(O[C@@H]2O[C@@H](C)[C@H](O)[C@H](O)[C@@H]2O)=C2C(=O)C=C(C3=CC=C(O)C(OC)=C3)OC2=C1

Calculated Properties

Physi-Chem Properties

Molecular Weight:	460.14	Volume:	438.949 ? Van der Waals volume.
Dense:	1.048	LogP:	1.512 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.796 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-2.985 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	5.0	Rigid Bonds:	24.0
TPSA:	148.05 ? Topological Polar Surface Area.	H-Bond Acceptor:	10.0
H-Bond Donor:	4.0	Rings:	4.0
Heavy Atoms:	10.0

MedChem Properties

QED Drug-Likeness Score:	0.44	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.83	Fsp³:	0.348
MCE-18:	86.387 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Rejected
Pfizer Rule:	Rejected	GSK Rule:	Accepted
Golden Triangle Rule:	Rejected	BMS Rule:	0
Chelating Alert:	1	PAINS Alert:	0
Colloidal aggregators:	0.592	Fluc inhibitor:	0.286 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.974 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.861 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.092	Promiscuous compounds:	0.345

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.811	MDCK Permeability:	-5.178
Pgp-inhibitor:	0.004	Pgp-substrate:	0.731
PAMPA:	0.931 ? The experimental data for Peff was logarithmically transformed (logPeff). Molecules with log Peff values below 2.0 were classified as low-permeability (Category 0), while those with log Peff values exceeding 2.5 were classified as high-permeability (Category 1).	Human Intestinal Absorption (HIA):	0.364
20% Bioavailability (F20%):	0.848	30% Bioavailability (F30%):	0.795
50% Bioavailability (F50%):	0.998

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.891
Plasma Protein Binding (PPB):	89.39%	Volume Distribution (VD):	-0.062
Fu:	12.387% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.992
OATP1B3 inhibitor:	0.999	BCRP inhibitor:	0.945
BSEP inhibitor:	0.218

ADMET: Metabolism

CYP1A2-inhibitor:	0.06	CYP1A2-substrate:	0.953
CYP2C19-inhibitor:	0.012	CYP2C19-substrate:	0.029
CYP2C9-inhibitor:	0.954	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.031	CYP2D6-substrate:	0.977
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.639
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.999
HLM stability:	0.359 ? Human liver microsomal (HLM) stability. Category 0: stable+ (HLM > 30 min); Category 1: unstable- (HLM ≤ 30 min). The output value is the probability of human liver microsomal instability, where a value closer to 1 indicates a higher likelihood of instability.

ADMET: Excretion

Clearance (CL):

3.093

Half-life (T1/2):

2.587

ADMET: Toxicity

hERG Blockers:	0.041	hERG Blockers (10um):	0.25
Human Hepatotoxicity (H-HT):	0.592	Drug-induced Liver Injury (DILI):	0.982
AMES Toxicity:	0.959	Rat Oral Acute Toxicity:	0.298
Maximum Recommended Daily Dose:	0.363	Skin Sensitization:	0.996
Carcinogencity:	0.563	Eye Corrosion:	0.001
Eye Irritation:	0.812	Respiratory Toxicity:	0.614
Drug-induced Neurotoxicity:	0.109	Ototoxicity:	0.453
Hematotoxicity:	0.658	Drug-induced Nephrotoxicity:	0.584
Genotoxicity:	0.92	RPMI-8226 Immunitoxicity:	0.277
A549 Cytotoxicity:	0.892	Hek293 Cytotoxicity:	0.731
BCF:	0.648 ? Bioconcentration factors are used for considering secondary poisoning potential and assessing risks to human health via the food chain. The unit is -log10[(mg/L)/(1000*MW)].	IGC50:	3.36 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.487 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.909 ? 96 hour fathead minnow LC50. The unit of LC50FM is -log10[(mg/L)/(1000*MW)].

Species Source

Organism ID	Organism Name	Taxonomy Level	Family	SuperKingdom	Isolation Part	Collection Location	Collection Time	Reference
NPO30700	Cassia nodosa	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO30700	Cassia nodosa	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]

Note for Reference:
In addition to directly collecting NP source organism data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated them from below databases:
☉ UNPD: Universal Natural Products Database [PMID: 23638153].
☉ StreptomeDB: a database of streptomycetes natural products [PMID: 33051671].
☉ TM-MC: a database of medicinal materials and chemical compounds in Northeast Asian traditional medicine [PMID: 26156871].
☉ TCM@Taiwan: a Traditional Chinese Medicine database [PMID: 21253603].
☉ TCMID: a Traditional Chinese Medicine database [PMID: 29106634].
☉ TCMSP: The traditional Chinese medicine systems pharmacology database and analysis platform [PMID: 24735618].
☉ HerDing: a herb recommendation system to treat diseases using genes and chemicals [PMID: 26980517].
☉ MetaboLights: a metabolomics database [PMID: 27010336].
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].

NP Quantity Composition/Concentration

Organism ID	Organism Name	Organism Material Preparation	Organism Part	NP Quantity (Standard)	NP Quantity (Minimum)	NP Quantity (Maximum)	Quantity Unit	Reference

Note for Reference:
In addition to directly collecting NP quantitative data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated NP quantitative records for specific NP domains (e.g., NPS from foods or herbs) from domain-specific databases. These databases include:
☉ DUKE: Dr. Duke's Phytochemical and Ethnobotanical Databases.
☉ PHENOL EXPLORER: is the first comprehensive database on polyphenol content in foods [PMID: 24103452], its homepage can be accessed at here.
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].

Biological Activity

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference

In vivo activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference

Experimental ADME

Experiment Model	Experiment Tissue	ADME Type	ADME Relation	ADME Value	ADME Unit	Reference

Experimental Toxicity

Quantitative toxicity

Experiment Model	Experiment Organism	Toxicity Type	Toxicity Relation	Toxicity Value	Toxicity Unit	Reference

Common Abbreviations:
LC: Lethal Concentration; LD: Lethal Dose; LT:Lethal Time; NOAEL: No-observed-adverse-effect Level; BMDL: Benchmark Dose Lower Confidence Limit; BMD: Benchmark Dose; BMC:Benchmark Concentration; LOAEL: Lowest Observed Adverse Effect Level; RfD:Reference Dose; RfC:Reference Concentration; MRL: Minimal Risk Level; MEG: Maximum Exposure Guideline; PAC: Protective Action Criteria

Categorical toxicity labels

Hepatotoxicity	Carcinogenicity	Mutagenicity	Cardiotoxicity	Respiratory Toxicity	Eye Irritation	Endocrine Disruption

Note for Reference:
In addition to directly collecting NP quantitative data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated NP toxicity records from domain-specific databases. These databases include:
☉ ToxValDB: a curated database that compiles quantitative toxicity values for chemicals from diverse public sources to support toxicological research and risk assessment.
☉ TOXRIC: a comprehensive, free-to-access, online database providing toxicological/feature data. The toxicity labels are retrieved from this database. [PMID: 36400569]

Chemically structural similarity

Similar Active Natural Products in NPASS

Top-200 similar NPs were calculated against the active-NP-set (includes approximately 50,000 NPs with experimentally-derived bioactivity available in NPASS)

Similarity is measured using the Tanimoto coefficient (Tc) , which compares the binary fingerprints of two molecules. Tc is calculated as the intersection divided by the union of '1' bits in the fingerprints, ranging from 0 to 1, with 1 indicating highest similarity.

● The left chart: Distribution of similarity level between NPC522614 and all remaining natural products in the NPASS database.
● The right table: Most similar natural products (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	20906
0.1-0.2	25157
0.2-0.3	2836
0.3-0.4	670
0.4-0.5	223
0.5-0.6	48
0.6-0.7	11
0.7-0.8	0
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.7468	Intermediate Similarity	NPC606560
0.6667	Remote Similarity	NPC610763
0.6627	Remote Similarity	NPC284960
0.6585	Remote Similarity	NPC182045
0.6548	Remote Similarity	NPC311830
0.642	Remote Similarity	NPC110349
0.6292	Remote Similarity	NPC129827
0.6163	Remote Similarity	NPC602805
0.6154	Remote Similarity	NPC475366
0.6098	Remote Similarity	NPC331652
0.6047	Remote Similarity	NPC601144
0.6024	Remote Similarity	NPC19709
0.5934	Remote Similarity	NPC473512
0.5895	Remote Similarity	NPC195257
0.5814	Remote Similarity	NPC222936
0.5814	Remote Similarity	NPC475942
0.5806	Remote Similarity	NPC284277
0.5795	Remote Similarity	NPC223747
0.5714	Remote Similarity	NPC295613
0.5658	Remote Similarity	NPC606105
0.5652	Remote Similarity	NPC15358
0.5647	Remote Similarity	NPC83283
0.5529	Remote Similarity	NPC473043
0.5506	Remote Similarity	NPC601710
0.5495	Remote Similarity	NPC4390
0.5474	Remote Similarity	NPC475497
0.5376	Remote Similarity	NPC473657
0.5341	Remote Similarity	NPC46420
0.5341	Remote Similarity	NPC271692
0.5325	Remote Similarity	NPC179126
0.5256	Remote Similarity	NPC137062
0.5222	Remote Similarity	NPC611303
0.5217	Remote Similarity	NPC479407
0.5217	Remote Similarity	NPC601586
0.5204	Remote Similarity	NPC209296
0.5195	Remote Similarity	NPC20830
0.5165	Remote Similarity	NPC22832
0.5165	Remote Similarity	NPC243930
0.5158	Remote Similarity	NPC44931
0.5114	Remote Similarity	NPC39360
0.5114	Remote Similarity	NPC249281
0.5114	Remote Similarity	NPC108831
0.5114	Remote Similarity	NPC29763
0.5114	Remote Similarity	NPC210003
0.5114	Remote Similarity	NPC238376
0.5114	Remote Similarity	NPC182634
0.5111	Remote Similarity	NPC27942
0.5109	Remote Similarity	NPC607707
0.5104	Remote Similarity	NPC22062
0.5104	Remote Similarity	NPC473634
0.5104	Remote Similarity	NPC210073
0.5104	Remote Similarity	NPC138811
0.5063	Remote Similarity	NPC47781
0.5056	Remote Similarity	NPC93337
0.5056	Remote Similarity	NPC168822
0.5056	Remote Similarity	NPC95090
0.5056	Remote Similarity	NPC27408
0.5056	Remote Similarity	NPC189142
0.5056	Remote Similarity	NPC77660
0.5054	Remote Similarity	NPC488072

Similar Clinical/Approved Drugs

Similarity level is defined by Tanimoto coefficient (Tc) between two molecules.

● The left chart: Distribution of similarity level between NPC522614 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	5174
0.1-0.2	3904
0.2-0.3	60
0.3-0.4	8
0.4-0.5	2
0.5-0.6	2
0.6-0.7	0
0.7-0.8	0
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Drug ID	Developmental Stage
0.5979	Remote Similarity	NPD7472	Pre-clinical
0.5204	Remote Similarity	NPD7054	Phase 4

Bioactivity similarity

Similar Natural Products in NPASS

Similarity level is defined by Bioactivity similarity was calculated based on bioactivity descriptors of compounds. The bioactivity descriptors were calculated by a recently developed AI algorithm Chemical Checker (CC) [Nature Biotechnology, 38:1087–1096, 2020; Nature Communications, 12:3932, 2021], which evaluated bioactivity similarities at five levels:
☉ A: chemistry similarity;
☉ B: biological targets similarity;
☉ C: networks similarity;
☉ D: cell-based bioactivity similarity;
☉ E: similarity based on clinical data.
Those 5 categories of CC bioactivity descriptors were calculated and then subjected to manifold projection using UMAP algorithm, to project all NPs on a 2-Dimensional space. The current NP was highlighted with a small circle in the 2-D map. Below figures: left-to-right, A-to-E.

A: chemistry similarity

B: biological targets similarity

C: networks similarity

D: cell-based bioactivity similarity

E: similarity based on clinical data